Transcutaneous medical device with variable stiffness

ABSTRACT

The present invention relates generally to variable stiffness transcutaneous medical devices including a distal portion designed to be more flexible than a proximal portion. The variable stiffness can be provided by a variable pitch in one or more wires of the device, a variable cross-section in one or more wires of the device, and/or a variable hardening and/or softening in one or more wires of the device.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/077,759, filed Mar. 10, 2005, which claims the benefit of U.S.Provisional Application No. 60/587,800 filed Jul. 13, 2004; each ofwhich is incorporated by reference herein in its entirety, and each ofwhich is hereby made a part of this specification.

FIELD OF THE INVENTION

The present invention relates generally to systems and methods for usewith partially implantable medical devices. More particularly, thepresent invention relates to systems and methods for use withtranscutaneous analyte sensors.

BACKGROUND OF THE INVENTION

Transcutaneous medical devices are useful in medicine for providing theenhanced functionality of a wholly implantable medical device whileavoiding many of the complications associated with a wholly implantabledevice. For example, transcutaneous analyte sensors are generallyminimally invasive compared to wholly implantable sensor, and arecapable of measuring an analyte concentration for a short period of time(e.g., three days) with similar accuracy as in a wholly implantablesensor.

SUMMARY OF THE INVENTION

In a first aspect, a transcutaneous analyte sensor is provided, thesensor comprising an elongated flexible portion, wherein the elongatedflexible portion has a variable stiffness along at least a portion ofits length.

In an embodiment of the first aspect, the sensor comprises at least onewire in a helical configuration, and wherein the variable stiffness isprovided by a variable pitch of the helical configuration.

In an embodiment of the first aspect, the sensor comprises at least onewire in a helical configuration, and wherein the variable stiffness isprovided by a variable cross-section of the wire.

In an embodiment of the first aspect, the sensor comprises at least onewire, and wherein the variable stiffness is provided by a variablehardness of the wire.

In an embodiment of the first aspect, the variable stiffness of theelongated flexible portion is produced by subjecting the wire to anannealing process.

In an embodiment of the first aspect, the sensor comprises at least onewire, the wire having a variable diameter.

In an embodiment of the first aspect, a distal portion of the sensor ismore flexible than a proximal portion of the sensor.

In an embodiment of the first aspect, an intermediate portion of thesensor is more flexible than at least one of a distal portion of thesensor and a proximal portion of the sensor.

In an embodiment of the first aspect, a distal tip of the sensor isstiffer than at least one of an intermediate portion of the sensor and aproximal portion of the sensor.

In a second aspect, a transcutaneous analyte sensor is provided, thesensor comprising a distal portion, an intermediate portion, and aproximal portion, wherein the distal portion is adapted to be insertedthrough a skin of a host, wherein the proximal portion is adapted toremain substantially external to the host when the distal portion isinserted in the host, and wherein a stiffness of the sensor is variablealong a length of the sensor.

In an embodiment of the second aspect, the proximal portion is stifferthan the distal portion.

In an embodiment of the second aspect, the sensor comprises at least onewire in a helical configuration, and wherein a difference in stiffnessof the distal portion and the proximal portion is provided by varying apitch of the helical configuration.

In an embodiment of the second aspect, the sensor comprises at least onewire in a helical configuration, and wherein a difference in flexibilityof the distal portion and the proximal portion is provided by a varyinga cross-section of the wire.

In an embodiment of the second aspect, the sensor comprises at least onewire, and wherein a difference in flexibility of the distal portion andthe proximal portion is provided by a varying a hardness of the wire.

In an embodiment of the second aspect, a variation in stiffness of theelongated flexible portion is produced by subjecting the wire to anannealing process.

In an embodiment of the second aspect, the intermediate portion is moreflexible than at least one of the distal portion and the proximalportion.

In an embodiment of the second aspect, the distal portion comprises adistal tip on an end of the sensor that is stiffer a substantial portionof the sensor.

In an embodiment of the second aspect, the intermediate portion is moreflexible than at least one of the distal portion and the proximalportion.

In an embodiment of the second aspect, the distal portion comprises adistal tip on an end of the sensor that is stiffer a substantial portionof the sensor.

In a third aspect, a transcutaneous analyte sensor is provided, thesensor comprising an in vivo portion adapted for insertion into a hostand an ex vivo portion adapted for operable connection to a device thatremains external to the host, wherein the sensor is configured to absorba relative movement between the ex vivo portion of the sensor and the invivo portion of the sensor.

In an embodiment of the third aspect, the sensor is configured to absorba relative movement by a flexibility of at least an intermediate portionlocated between the in vivo portion and the ex vivo portion.

In an embodiment of the third aspect, the device comprises a housingadapted for mounting on a skin of a host, wherein the housing compriseselectrical contacts operably connected to the sensor.

In an embodiment of the third aspect, the ex vivo portion of the sensoris has a preselected stiffness to maintain a stable connection betweenthe sensor and the electrical contacts.

In an embodiment of the third aspect, the in vivo portion of the sensorhas a preselected flexibility to minimize mechanical stresses caused bymotion of the host.

In an embodiment of the third aspect, a stiffness of the ex vivo portionof the sensor is greater than a stiffness of the in vivo portion of thesensor.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a perspective view of a transcutaneous sensor assembly.

FIG. 1B is a side cross-sectional view of the transcutaneous sensorassembly of FIG. 1A.

FIG. 2 is a schematic side view of a transcutaneous medical device.

FIG. 3A is a schematic side view of a first transcutaneous medicaldevice having a variable stiffness.

FIG. 3B is a schematic side view of a second transcutaneous medicaldevice having a variable stiffness.

FIG. 3C is a schematic side view of a third transcutaneous medicaldevice having a variable stiffness.

FIGS. 4A to 4D are perspective and side views of a first variablestiffness wire for use with a transcutaneous analyte sensor.

FIGS. 5A and 5B are perspective and cross-sectional views of a secondvariable stiffness wire for use with a transcutaneous analyte sensor.

FIGS. 6A and 6B are perspective and cross-sectional views of a thirdvariable stiffness wire suitable for use with a transcutaneous analytesensor.

FIG. 7 is an expanded view of distal and proximal portions of atranscutaneous sensor in one example.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The following description and examples illustrate some exemplaryembodiments of the disclosed invention in detail. Those of skill in theart will recognize that there are numerous variations and modificationsof this invention that are encompassed by its scope. Accordingly, thedescription of a certain exemplary embodiment should not be deemed tolimit the scope of the present invention.

DEFINITIONS

In order to facilitate an understanding of the preferred embodiments, anumber of terms are defined below.

The term “analyte” as used herein is a broad term and is used in itsordinary sense, including, without limitation, to refer to a substanceor chemical constituent in a biological fluid (for example, blood,interstitial fluid, cerebral spinal fluid, lymph fluid or urine) thatcan be analyzed. Analytes can include naturally occurring substances,artificial substances, metabolites, and/or reaction products. In someembodiments, the analyte for measurement by the sensing regions,devices, and methods is glucose. However, other analytes arecontemplated as well, including but not limited to acarboxyprothrombin;acylcarnitine; adenine phosphoribosyl transferase; adenosine deaminase;albumin; alpha-fetoprotein; amino acid profiles (arginine (Krebs cycle),histidine/urocanic acid, homocysteine, phenylalanine/tyrosine,tryptophan); andrenostenedione; antipyrine; arabinitol enantiomers;arginase; benzoylecgonine (cocaine); biotinidase; biopterin; c-reactiveprotein; carnitine; carnosinase; CD4; ceruloplasmin; chenodeoxycholicacid; chloroquine; cholesterol; cholinesterase; conjugated1-.beta.hydroxy-cholic acid; cortisol; creatine kinase; creatine kinaseMM isoenzyme; cyclosporin A; d-penicillamine; de-ethylchloroquine;dehydroepiandrosterone sulfate; DNA (acetylator polymorphism, alcoholdehydrogenase, alpha 1-antitrypsin, cystic fibrosis, Duchenne/Beckermuscular dystrophy, glucose-6-phosphate dehydrogenase, hemoglobin A,hemoglobin S, hemoglobin C, hemoglobin D, hemoglobin E, hemoglobin F.D-Punjab, beta-thalassemia, hepatitis B virus, HCMV, HIV-1, HTLV-1,Leber hereditary optic neuropathy, MCAD, RNA, PKU, Plasmodium vivax,sexual differentiation, 21-deoxycortisol); desbutylhalofantrine;dihydropteridine reductase; diptheria/tetanus antitoxin; erythrocytearginase; erythrocyte protoporphyrin; esterase D; fattyacids/acylglycines; free .beta.-human chorionic gonadotropin; freeerythrocyte porphyrin; free thyroxine (FT4); free tri-iodothyronine(FT3); fumarylacetoacetase; galactose/gal-1-phosphate;galactose-1-phosphate uridyltransferase; gentamicin; glucose-6-phosphatedehydrogenase; glutathione; glutathione perioxidase; glycocholic acid;glycosylated hemoglobin; halofantrine; hemoglobin variants;hexosaminidase A; human erythrocyte carbonic anhydrase I;17-alpha-hydroxyprogesterone; hypoxanthine phosphoribosyl transferase;immunoreactive trypsin; lactate; lead; lipoproteins ((a), B/A-1, beta.);lysozyme; mefloquine; netilmicin; phenobarbitone; phenytoin;phytanic/pristanic acid; progesterone; prolactin; prolidase; purinenucleoside phosphorylase; quinine; reverse tri-iodothyronine (rT3);selenium; serum pancreatic lipase; sissomicin; somatomedin C; specificantibodies (adenovirus, anti-nuclear antibody, anti-zeta antibody,arbovirus, Aujeszky's disease virus, dengue virus, Dracunculusmedinensis, Echinococcus granulosus, Entamoeba histolytica, enterovirus,Giardia duodenalisa, Helicobacter pylori, hepatitis B virus, herpesvirus, HIV-1, IgE (atopic disease), influenza virus, Leishmaniadonovani, leptospira, measles/mumps/rubella, Mycobacterium leprae,Mycoplasma pneumoniae, Myoglobin, Onchocerca volvulus, parainfluenzavirus, Plasmodium falciparum, poliovirus, Pseudomonas aeruginosa,respiratory syncytial virus, rickettsia (scrub typhus), Schistosomamansoni, Toxoplasma gondii, Trepenoma pallidium, Trypanosomacruzi/rangeli, vesicular stomatis virus, Wuchereria bancrofti, yellowfever virus); specific antigens (hepatitis B virus, HIV-1);succinylacetone; sulfadoxine; theophylline; thyrotropin (TSH); thyroxine(T4); thyroxine-binding globulin; trace elements; transferrin;UDP-galactose-4-epimerase; urea; uroporphyrinogen I synthase; vitamin A;white blood cells; and zinc protoporphyrin. Salts, sugar, protein, fat,vitamins and hormones naturally occurring in blood or interstitialfluids can also constitute analytes in certain embodiments. The analytecan be naturally present in the biological fluid, for example, ametabolic product, a hormone, an antigen, an antibody, and the like.Alternatively, the analyte can be introduced into the body, for example,a contrast agent for imaging, a radioisotope, a chemical agent, afluorocarbon-based synthetic blood, or a drug or pharmaceuticalcomposition, including but not limited to insulin; ethanol; cannabis(marijuana, tetrahydrocannabinol, hashish); inhalants (nitrous oxide,amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine(crack cocaine); stimulants (amphetamines, methamphetamines, Ritalin,Cylert, Preludin, Didrex, PreState, Voranil, Sandrex, Plegine);depressants (barbituates, methaqualone, tranquilizers such as Valium,Librium, Miltown, Serax, Equanil, Tranxene); hallucinogens(phencyclidine, lysergic acid, mescaline, peyote, psilocybin); narcotics(heroin, codeine, morphine, opium, meperidine, Percocet, Percodan,Tussionex, Fentanyl, Darvon, Talwin, Lomotil); designer drugs (analogsof fentanyl, meperidine, amphetamines, methamphetamines, andphencyclidine, for example, Ecstasy); anabolic steroids; and nicotine.The metabolic products of drugs and pharmaceutical compositions are alsocontemplated analytes. Analytes such as neurochemicals and otherchemicals generated within the body can also be analyzed, such as, forexample, ascorbic acid, uric acid, dopamine, noradrenaline,3-methoxytyramine (3MT), 3,4-dihydroxyphenylacetic acid (DOPAC),homovanillic acid (HVA), 5-hydroxytryptamine (5HT), and5-hydroxyindoleacetic acid (FHIAA).

The terms “operably connected” and “operably linked” as used herein arebroad terms and are used in their ordinary sense, including, withoutlimitation, to refer to one or more components linked to one or moreother components. The terms can refer to a mechanical connection, anelectrical connection, or a connection that allows transmission ofsignals between the components. For example, one or more electrodes canbe used to detect the amount of analyte in a sample and to convert thatinformation into a signal; the signal can then be transmitted to acircuit. In such an example, the electrode is “operably linked” to theelectronic circuitry.

The term “host” as used herein is a broad term and is used in itsordinary sense, including, without limitation, to refer to mammals,particularly humans.

The term “exit-site” as used herein is a broad term and is used in itsordinary sense, including, without limitation, to refer to the areawhere a medical device (for example, a sensor arid/or needle) exits fromthe host's body.

The phrase “continuous (or continual) analyte sensing” as used herein isa broad term and is used in its ordinary sense, including, withoutlimitation, to refer to the period in which monitoring of analyteconcentration is continuously, continually, and or intermittently(regularly or irregularly) performed, for example, about every 5 to 10minutes.

The term “electrochemically reactive surface” as used herein is a broadterm and is used in its ordinary sense, including, without limitation,to refer to the surface of an electrode where an electrochemicalreaction takes place. For example, a working electrode measures hydrogenperoxide produced by the enzyme-catalyzed reaction of the analytedetected, which reacts to create an electric current. Glucose analytecan be detected utilizing glucose oxidase, which produces H₂O₂ as abyproduct. H₂O₂ reacts with the surface of the working electrode,producing two protons (2H⁺), two electrons (2e⁻) and one molecule ofoxygen (O₂), which produces the electronic current being detected. Inthe case of the counter electrode, a reducible species, for example, O₂is reduced at the electrode surface in order to balance the currentbeing generated by the working electrode.

The term “sensing region” as used herein is a broad term and is used inits ordinary sense, including, without limitation, to refer to theregion of a monitoring device responsible for the detection of aparticular analyte. The sensing region generally comprises anon-conductive body, a working electrode (anode), a reference electrode(optional), and/or a counter electrode (cathode) passing through andsecured within the body forming electrochemically reactive surfaces onthe body and an electronic connective means at another location on thebody, and a multi-domain membrane affixed to the body and covering theelectrochemically reactive surface.

The terms “electronic connection” and “electrical connection” as usedherein is a broad term and is used in its ordinary sense, including,without limitation, to refer to any electronic connection known to thosein the art that can be utilized to interface the sensing regionelectrodes with the electronic circuitry of a device, such as mechanical(for example, pin and socket) or soldered electronic connections.

The term “domain” as used herein is a broad term and is used in itsordinary sense, including, without limitation, to refer to a region ofthe membrane system that can be a layer, a uniform or non-uniformgradient (for example, an anisotropic region of a membrane), or aportion of a membrane.

The term “distal to” as used herein is a broad term and is used in itsordinary sense, including, without limitation, the spatial relationshipbetween various elements in comparison to a particular point ofreference.

The term “proximal to” as used herein is a broad term and is used in itsordinary sense, including, without limitation, the spatial relationshipbetween various elements in comparison to a particular point ofreference.

The terms “in vivo portion” and “distal portion” as used herein arebroad terms and are used in their ordinary sense, including, withoutlimitation, to refer to the portion of the device (for example, asensor) adapted for insertion into and/or existence within a living bodyof a host.

The terms “ex vivo portion” and “proximal portion” as used herein arebroad terms and are used in their ordinary sense, including, withoutlimitation, to refer to the portion of the device (for example, asensor) adapted to remain and/or exist outside of a living body of ahost.

The term “intermediate portion” as used herein is a broad term and isused in its ordinary sense, including, without limitation, to refer to aportion of the device between a distal portion and a proximal portion.

The terms “transdermal” and “transcutaneous” as used herein are broadterms and is used in their ordinary sense, including, withoutlimitation, to refer to extending through the skin of a host. Forexample, a transdermal analyte sensor is one that extends through theskin of a host.

The term “hardening” as used herein is a broad term and is used in itsordinary sense, including, without limitation, to refer to an increasein hardness of a metal induced by a process such as hammering, rolling,drawing, or the like.

The term “softening” as used herein is a broad term and is used in itsordinary sense, including, without limitation, to refer to an increasein softness of a metal induced by processes such as annealing,tempering, or the like.

The term “tempering” as used herein is a broad term and is used in itsordinary sense, including, without limitation, to refer to theheat-treating of metal alloys, particularly steel, to reduce brittlenessand restore ductility.

The term “annealing” as used herein is a broad term and is used in itsordinary sense, including, without limitation, to refer to the treatmentof a metal or alloy by heating to a predetermined temperature, holdingfor a certain time, and then cooling to room temperature to improveductility and reduce brittleness.

The term “stiff” as used herein is a broad term and is used in itsordinary sense, including, without limitation, to refer to a materialnot easily bent, lacking in suppleness or responsiveness. In thepreferred embodiments, the degree of stiffness can be relative to otherportions of the device.

The term “flexible” as used herein is a broad term and is used in itsordinary sense, including, without limitation, to refer to a materialthat is bendable, pliable, or yielding to influence. In the preferredembodiments, the degree of flexibility can be relative to other portionsof the device.

The devices of the preferred embodiments include transdermal medicaldevices, such as transcutaneous sensor assemblies, with variablestiffness configured along at least a portion of the device. In oneaspect of the preferred embodiments, a transcutaneous sensor assembly isprovided, including a sensor for sensing an analyte linked to a housingfor mounting on the skin of the host. The housing houses an electronicsunit associated with the sensor and is adapted for secure adhesion tothe host's skin.

Transcutaneous Sensors

FIGS. 1A and 1B are perspective and side cross-sectional views of atranscutaneous sensor assembly 10 of a preferred embodiment. The sensorsystem includes a housing 12 and preferably includes an adhesivematerial 14 on its backside 16 for adhesion to a host's skin. A sensor18 extends from the housing and is adapted for transdermal insertionthrough the skin of the host. The sensor portion can be configured forinsertion into a variety of in vivo locations, including subcutaneous,venous, or arterial locations, for example. One or more contacts 22 areconfigured to provide secure electrical contact between sensor 18 and anelectronics unit 20. The housing 12 is designed to maintain theintegrity of the sensor in the host so as to reduce or eliminatetranslation of motion between the housing 12, the host, and/or thesensor 18.

In general, the sensor includes at least one electrode configured formeasuring an analyte. In one embodiment, the sensor 18 includes at leasttwo electrodes: a working electrode and at least one additionalelectrode, which can function as a counter and/or reference electrode.Preferably, the working electrode comprises a wire formed from aconductive material, such as platinum, palladium, graphite, gold,carbon, conductive polymer, or the like. In some embodiments, the wireis formed from a bulk material, or alternatively, a composite of two ormore metals and/or insulators (e.g., platinum plated steel). The workingelectrode is configured to measure the concentration of an analyte. Thereference electrode, which can function as a reference electrode alone,or as a dual reference and counter electrode, is preferably formed fromsilver, silver/silver chloride, or the like. In preferred embodiments,the reference electrode is twisted with or around the working electrode;however other configurations for the working electrode and the referenceelectrode are also possible, for example juxtapositioned, adjacent,coaxial, concentric, interdigitated, spiral-wound, or the like.

In some alternative embodiments, additional electrodes can be includedwithin the assembly. For example, a three-electrode system (working,reference, and counter electrodes) and/or a system including anadditional working electrode (which can be used to generate oxygen orcan be configured as a baseline subtracting electrode, for example) canbe employed. Other sensor/wire/electrode configurations (for exampleone, two, three, four, or more wires and/or electrode configurations)are also within the scope of the preferred embodiments. For example,U.S. Pat. No. 6,613,379 to Ward et al. describes a bundle of wiresaround which a counter electrode is deposed and configured for measuringan analyte, and U.S. Pat. No. 6,329,161 to Heller et al. describes asingle wire electrode configured for measuring an analyte. Any suchconfiguration adapted for transcutaneous analyte measurement can beconfigured with a variable stiffness in accordance with the preferredembodiments.

In some embodiments (for example, enzymatic-based sensors), a membranesystem is disposed over some or all of the electroactive surfaces of thesensor 18 (working and/or reference electrodes) and provides one or moreof the following functions: 1) protection of the exposed electrodesurface from the biological environment; 2) diffusion resistance(limitation) of the analyte; 3) a catalyst for enabling an enzymaticreaction; 4) hindering or blocking passage of interfering species; and5) hydrophilicity at the electrochemically reactive surfaces of thesensor interface, such as is described in U.S. patent application Ser.No. 11/077,715, filed on Mar. 10, 2005 and entitled “TRANSCUTANEOUSANALYTE SENSOR”.

The electronics unit 20 can be integral with or removably attached tothe housing 12, and includes hardware, firmware and/or software thatenable measurement of levels of the analyte via the sensor 18. Forexample, the electronics unit 20 comprises a potentiostat, a powersource for providing power to the sensor, other components useful forsignal processing, and preferably an RF module for transmitting datafrom the electronics unit 20 to a receiver. Electronics can be affixedto a printed circuit board (PCB), or the like, and can take a variety offorms. For example, the electronics can take the form of an integratedcircuit (IC), such as an application-specific integrated circuit (ASIC),a microcontroller, or a processor. Preferably, the electronics unit 20houses the sensor electronics, which comprise systems and methods forprocessing sensor analyte data. Examples of systems and methods forprocessing sensor analyte data are described in more detail below and inco-pending U.S. application Ser. No. 10/633,367 filed Aug. 1, 2003entitled, “SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA.”

U.S. patent application Ser. No. 11/077,715, filed on Mar. 10, 2005, andentitled, “TRANSCUTANEOUS ANALYTE SENSOR,” describes an embodiment of atranscutaneous analyte sensor that benefits from variable stiffness.Variable stiffness configurations along at least a portion of the devicecan be employed with devices such as are described in U.S. Pat. No.6,613,379 to Ward et al., U.S. Pat. No. 6,122,536 to Sun et al., U.S.Pat. No. 6,329,161 to Heller et al., U.S. Pat. No. 6,477,395 toSchulman, and U.S. Pat. No. 4,671,288 to Gough.

Variable Stiffness

Conventional transcutaneous devices can be subject to motion artifactassociated with host movement when the host is using the device. Forexample, in the example of a transcutaneous analyte sensor such asdescribed above, various movements on the sensor (for example, relativemovement within and between the subcutaneous space, dermis, skin, andexternal portions of the sensor) create stresses on the device, whichare known to produce artifacts on the sensor signal.

Accordingly, the design considerations (for example, stressconsiderations) vary for different sections of a transcutaneous medicaldevice. For example, certain portions of the device can benefit ingeneral from greater flexibility as the portion of the device encountersgreater mechanical stresses caused by movement of the tissue within thepatient and relative movement between the in vivo and ex vivo portionsof the sensor. Additionally or alternatively, certain portions of thedevice can benefit in general from a stiffer, more robust design toensure structural integrity and/or reliable electrical connections.Additionally, in some embodiments wherein an insertion device (forexample, needle that aids in insertion) is retracted over the device, astiffer design can enable minimized crimping and/or easy retraction.Thus, by designing greater flexibility into the some portions of thedevice, the flexibility can compensate for movement and noise associatedtherewith; and by designing greater stiffness into other portions,column strength (for retraction of the needle over the sensor),electrical connections, and structural integrity can be enhanced.

FIG. 2 is a side schematic view of a transcutaneous medical device 34,such as illustrated as the transcutaneous analyte sensor 18 of FIG. 1.In general, a transcutaneous medical device 34, can be divided intothree zones, a proximal portion 24 with a proximal tip 26, a distalportion 28 with a distal tip 30, and an intermediate portion 32. Thepreferred embodiments can employ a variety of configurations thatprovide variable stiffness along at least a portion of the device inorder to overcome disadvantages of conventional transcutaneous devices.Although the following description is focused on an embodiment of atranscutaneous analyte sensor, one skilled in the art can appreciatethat the variable stiffness of the preferred embodiments can beimplemented with a variety of transcutaneous medical devices.

Generally, the proximal portion 24 is adapted to remain above the host'sskin after device insertion and operably connects to a housing ex vivo,for example. The proximal portion 24 typically provides the mechanicaland/or electrical connections of the device to housings, electronics, orthe like. The proximal portion includes a proximal tip 26 on an endthereof. It is noted that the terms “proximal portion,” “ex vivoportion,” and “proximal tip” do not necessarily imply an exact length orsection, rather is generally a section that is more proximal than distalrelative to the housing. In some embodiments, the proximal portion (orproximal tip) is stiffer than at least one of the intermediate anddistal portions.

Generally, the distal portion 28 of the sensor is adapted for insertionunder the host's skin, and is also referred to as the in vivo portion.The distal portion 28 typically provides the device function in vivo,and therefore encounters stresses caused by insertion of the device intothe host's tissue and subsequent movement of the tissue of the patient.The distal portion includes a distal tip 30 on an end thereof. It isnoted that the terms “distal portion,” “in vivo portion,” and “distaltip” do not necessarily imply an exact length or section, rather isgenerally a section that is more distal than proximal relative to thehousing. In some embodiments, the distal portion is more flexible thanat least one of the intermediate and proximal portions. In someembodiments, the distal tip is less flexible than at least one of theremaining (non-tip) distal portion, the intermediate portion, and theproximal portion.

Generally, the intermediate portion 32 is located between the proximalportion 24 and the distal portion and may include portions adapted forinsertion or adapted to remain above the skin. The intermediate portion32 typically provides a transition between the in vivo and ex vivoportions, and can incur stresses caused by relative movement between thein vivo and ex vivo portions of the sensor, for example. It is notedthat the term “intermediate portion” does not necessarily imply an exactlength or section, rather is generally a section that in-between theproximal and distal portions. In some embodiments, the intermediateportion is more flexible than one or both of the distal and proximalportions.

FIG. 3A is a side schematic view of a transcutaneous medical device 34 ain one embodiment adapted for insertion through the skin of a host. Inthis embodiment, the device 34 a is designed with greater flexibilitygenerally in a distal portion 28 (relative to intermediate and/orproximal portions), which is illustrated by light cross-hatching in thedistal portion of the device. Stated in another way, the device isdesigned with a greater stiffness generally in the proximal portion 24than the intermediate and/or the distal portions, which is illustratedby heavy cross-hatching in the proximal portion 24 of the device. Insome embodiments, the intermediate portion includes a flexibilitysubstantially similar to that of the distal portion; in otherembodiments, the intermediate portion gradually transitions between theflexibility of the distal portion and the stiffness of the proximalportion. For example, in situations wherein movement of the tissuewithin the patient and relative movement between the in vivo and ex vivoportions of the device create stresses on the device, greaterflexibility in a distal portion (relative to intermediate and/orproximal portions) can provide relief from these mechanical stresses,protecting both the integrity of the sensor and the host tissue.Additionally or alternatively, in situations wherein mechanical and/orelectrical connections are required for accurate device function,greater stiffness in the proximal portion 24 (and/or the proximal tip)of the device can increase the stability and reliability of theseconnections. Thus, the ex-vivo or proximal portion 24 of the sensor isconfigured for stable connection to the electronics and can additionallybe configured to receive an insertion device (such as a needle that aidsin sensor insertion) upon retraction from the skin of the host (see U.S.patent application Ser. No. 11/077,715, filed on Mar. 10, 2005 andentitled “TRANSCUTANEOUS ANALYTE SENSOR”).

FIG. 3B is a side schematic view of a transcutaneous medical device 34 bof a preferred embodiment adapted to be inserted through the skin of ahost. In this embodiment, the device is designed with an increasedstiffness at a distal tip 30 (or a distal portion 28) of the device(relative to intermediate and/or proximal portions) in order to provideincreased strength and/or structural integrity to the tip, which isillustrated by heavy cross-hatching. In some situations, the device isinserted into the host such that a tunnel is formed therein. When thedevice abuts the tunnel end, increased stress to the distal tip canoccur. This increased stress can cause the device to bend, resulting inmalfunctioning of the device.

In some embodiments, this increased stiffness is designed into thedevice by creating a greater hardness of the distal tip of the device,for example, by annealing or coating the device. In one embodiment of atranscutaneous analyte sensor as described above with reference to FIG.1, a higher pitch of the helically wound reference electrode for atleast a few windings at a distal end of the reference electrode createsa relative stiffness of the distal portion or tip of the device. It isbelieved that a stiffer distal portion or tip advantageously providesincreased stability, column strength, and proper placement of the devicein the host.

FIG. 3C is a side schematic view of a transcutaneous medical device 34 cin yet another embodiment adapted to be inserted through the skin of ahost. In this embodiment, the device 34 c is designed with an increasedflexibility at an intermediate portion 32 thereof. Namely, theintermediate portion of the device is designed to absorb shock betweenthe proximal and distal portions, for example, such that movement of theex vivo portion of the device does not substantially translate to the invivo portion of the device (and vice versa). In some aspects of thisembodiment, the distal portion is designed with a flexibility similar tothat of the intermediate portion. In some aspects of this embodiment,the flexibility gradually changes from the distal portion to theproximal portion, including a relatively flexible intermediate portion32.

In some embodiments, any combination of the above described relativelystiff or flexible portions can be designed into a transcutaneous medicaldevice. In fact, a variety of additional stiff and/or flexible portionscan be incorporated into the distal and/or proximal portions of thedevice without departing from the scope of the preferred embodiments.The flexibility and/or stiffness can be stepped, gradual, or anycombination thereof.

The variable stiffness (flexibility) of the preferred embodiments can beprovided by a variable pitch of any one or more wires of the device, avariable cross-section of any one or more wires of the device, and/or avariable hardening and/or softening of any one or more wires of thedevice, for example, as is described in more detail below.

FIGS. 4A to 4D are perspective and side views of a variable stiffnesswire used in a transcutaneous medical device, such as an analyte sensor.In FIG. 4A, a wire 36 is shown, which can represent the workingelectrode or reference electrode of the embodiment described withreference to FIG. 1, for example. Alternatively, the wire 36 canrepresent one or more wires of a multiple wire sensor (examples of eachare described above). The variable stiffness wire described herein canbe employed in a transcutaneous medical device to provide variablestiffness along a portion of the length of the device, such as in ananalyte sensor.

FIG. 4B is a side view of a variable stiffness wire 36 b whereinphysical processing of the distal, intermediate, and/or proximalportions of the wire provide for variability of the stiffness of thewire. In some embodiments, some portion (for example, the distalportion) of the wire is softened using a process such as annealing ortempering. In some embodiments, some portion (for example, the proximalportion) of the wire is hardened using a process such as drawing orrolling. In some embodiments, some combination of softening andhardening as described herein are employed to provide variable stiffnessof the wire. In the embodiment described with reference to FIG. 1,including a working electrode and a reference electrode, the workingelectrode can be hardened and/or softened to provide for the variablestiffness of one or more portions of the device, such as is described inmore detail elsewhere herein. Another alternative embodiment provides avarying modulus of elasticity of the material to provide the variablestiffness of the preferred embodiments.

FIG. 4C is a side view of an alternative variable stiffness wire 36 c,wherein the wire has a gradually increasing or decreasing diameter alongits length. The variability in diameter can be produced by physical orchemical processes, for example, by grinding, machining, rolling,pulling, etching, drawing, swaging, or the like. In this way, atranscutaneous analyte sensor, or other transcutaneous medical device,can be produced having a variable stiffness. In the embodiment describedwith reference to FIG. 1, for example, including a working electrode anda reference electrode, the working electrode can be formed with avariable diameter to provide for the variable stiffness of one or moreportions of the device, such as described in more detail elsewhereherein.

FIG. 4D is a side view of another alternative variable stiffness wire 36d, wherein the wire is step increased or decreased to provide two (ormore) different flexibilities of the wire. The wire can be stepped byphysical or chemical processes known in the art, such as described withreference to FIG. 4C. In this way, a transcutaneous analyte sensor, orother transcutaneous medical device, can be produced with a variablestiffness. A noted advantage of the smaller diameter configurations ofFIGS. 4C and 4D include reduced sizing of the in vivo portion of thedevice, which is believed to be more comfortable for the patient and toinduce less invasive trauma around the device, thereby providing anoptimized device design.

FIGS. 5A and 5B are perspective and cross-sectional views of a variablestiffness wire 38 in an alternative embodiment representing any one ormore wires associated with a transcutaneous medical device, such as ananalyte sensor. For example, the wire 38 can represent the referenceelectrode of the embodiment described with reference to FIG. 1.Alternatively, the wire 38 can represent the wire of a single ormultiple wire sensor (examples of each are described above).

In this embodiment, two distinct portions 40, 42 are shown with firstand second pitches; however, the illustration is not meant to belimiting and the variable pitch can include any number of gradualportions, stepped portions, or the like. Additionally, the variablepitch and/or helical configuration can be provided on only a portion ofthe wire or on the entire length of the wire, and can include any numberof pitch changes. In this embodiment, a first portion 40 is wound tohave relatively closely spaced coils, namely, a high helix pitch,whereas a second 42 portion is not subjected to high stress levels andcan include coils wound with a lower helix pitch. The helix pitch isdefined as the number of coils of the wire core per unit length of thedevice, or the distance between the coils.

FIG. 5B is a cross-sectional view along line B-B of the device of FIG.5A, illustrating a first distance d₁ between the coils in the firstportion 40 and a second distance d₂ between the coils in the secondportion 42, wherein d₂ is greater than d₁. Thus, the wire has a variablestiffness attributable to the varying helix pitch over the length of thesensor. In this way, portions of a device having wire with a low helixpitch are designed with greater flexibility and are more able to handlethe stresses associated with motion of the sensor while portions of thesensor having wire with a high helix pitch are designed with morestiffness and provide more stability for the sensor in the housing. Anyportions (proximal, intermediate, and/or distal portions (or tips)) canbe designed with a variable pitch to impart variable stiffness.

FIGS. 6A and 6B are perspective and longitudinal views of a variablestiffness wire 44 in yet another alternative embodiment representing anyone or more wires associated with a transcutaneous medical device, suchas an analyte sensor. For example, the wire 44 can be the referenceelectrode of the embodiment described with reference to FIG. 1.Alternatively, the wire 44 can be a working electrode, and/or one ormore wires of a multiple wire sensor (examples of each are describedabove).

In this embodiment, two distinct portions 46, 48 are shown with firstand second wire diameters that provide a variable cross-section;however, the illustration is not meant to be limiting and the variablecross-section can be gradual, stepped, or the like. Additionally, thevariable cross-section and/or helical configuration can be provided ononly a portion of the wire or on the entire length of the wire, and caninclude any number of cross-section changes. In this embodiment, thehelically wound wire is designed with a variable cross-sectional areaover the length of the sensor from a small cross-sectional area in thefirst portion 46 to a larger cross-sectional area in the second portion48.

FIG. 6B is a cross-sectional view along line B-B of the device of FIG.6A, revealing cross-sectional information about one or more wires thatmake up the coil, including a first cross-section x, of the wire in thefirst portion 20 and a second cross-section x₂ of the wire in the secondportion 48, wherein x₂ is greater than x₁. Thus, the device of thisembodiment has a variable stiffness attributable to the varyingcross-section over the length of the sensor. In this way, first portion46 has a smaller cross-sectional area and is therefore more flexible andcapable of withstanding the stresses associated with patient movement,for example; while the second portion 48 has a larger cross-sectionalarea and is stiffer and provides more stability and column strengthdesirable for mechanical and electrical connections, for example.

The transcutaneous analyte sensor of FIG. 1 includes a helicalconfiguration. The helical surface topography of the reference electrodesurrounding the working electrode not only provides electrochemicalfunctionality, but can also provide anchoring within the host tissue.The device preferably remains substantially stationary within the tissueof the host, such that migration or motion of the sensor with respect tothe surrounding tissue is minimized. Migration or motion can causeinflammation at the sensor implant site due to irritation and can alsocause noise on the sensor signal due to motion-related artifact, forexample. Therefore, it can be advantageous to provide an anchoringmechanism that provides support for the sensor in vivo portion to avoidor minimize the above-mentioned problems. Combining advantageous sensorgeometry with advantageous anchoring minimizes additional parts in thedevice, and allows for an optimally small or low profile design of thesensor. Additionally or alternatively, anchoring can be provided byprongs, spines, barbs, wings, hooks, rough surface topography, graduallychanging diameter, or the like, which can be used alone or incombination with the helical surface topography to stabilize the sensorwithin the subcutaneous tissue.

EXAMPLE

FIG. 7 is an expanded view of distal and proximal portions of atranscutaneous sensor 50 in one example. FIG. 7 illustrates a sensor 50broken away between its distal portion 52 and proximal portion 54,representing any length or configuration there between. In theillustrated embodiment, the sensor 50 includes two electrodes: a workingelectrode 56 and one additional electrode, which can function as acounter and/or reference electrode, hereinafter referred to as thereference electrode 58. Each electrode is formed from a fine wire with adiameter of approximately 0.0045 inches.

The working electrode 56 comprises a platinum wire and is configured andarranged to measure the concentration of an analyte. In this example ofan enzymatic electrochemical sensor, the working electrode measures thehydrogen peroxide produced by an enzyme catalyzed reaction of theanalyte being detected and creates a measurable electronic current (forexample, detection of glucose utilizing glucose oxidase produces H₂O₂peroxide as a by product, H₂O₂ reacts with the surface of the workingelectrode producing two protons (2H⁺), two electrons (2e⁻) and onemolecule of oxygen (O₂) which produces the electronic current beingdetected).

The working electrode 56 is covered with an insulator 57, e.g.,Parylene, which is vapor-deposited on the working electrode. Parylene isan advantageous conformal coating because of its strength, lubricity,and electrical insulation properties; however, a variety of otherinsulating materials can also be used, for example, fluorinatedpolymers, polyethyleneterephthalate, polyurethane, polyimide, or thelike. The reference electrode 58, which can function as a counterelectrode alone, or as a dual reference and counter electrode, ispreferably silver or a silver-containing material. In this example, thereference electrode 58 is helically twisted around the working electrode56. A window 55 is formed on the insulating material to expose anelectroactive surface of the working electrode 56. Other methods andconfigurations for exposing electroactive surfaces can also be employed.

In this example, the reference electrode 58 is wound with a variablepitch that creates a variable stiffness along the length of the sensor50. Namely, the sensor 50 is designed with a greater stiffness generallyin the proximal portion 54 than the intermediate and/or the distalportions 52. However, an increased stiffness of a section of the distalportion 52, shown adjacent to the window 55 wherein the referenceelectrode 58 includes a higher helix pitch for a few windings, providesincreased strength in a high stress location, without inhibiting theoverall flexibility of the distal portion 52. It is believed that insituations wherein movement of the tissue within the patient andrelative movement between the in vivo and ex vivo portions of the devicecreate stresses on the device, greater flexibility in a distal portion(and optionally in the intermediate portion relative to the proximalportion) can provide relief from these mechanical stresses, protectingboth the integrity of the sensor and the host tissue. Additionally oralternatively, in situations wherein mechanical and/or electricalconnections are employed for accurate function, greater stiffness in theproximal portion (and/or the proximal tip) of the device can increasethe stability and reliability of these connections. Additionally, thisexemplary configuration is advantageous for the reasons described above,and further provides an enhanced mechanical stability by thedistribution of forces of the helical wire along the straight wire.

Methods and devices that are suitable for use in conjunction withaspects of the preferred embodiments are disclosed in U.S. Pat. No.4,994,167 issued Feb. 19, 1991 and entitled “BIOLOGICAL FLUID MEASURINGDEVICE”; U.S. Pat. No. 4,757,022 issued Feb. Jul. 12, 1988 and entitled“BIOLOGICAL FLUID MEASURING DEVICE”; U.S. Pat. No. 6,001,067 issued Feb.Dec. 14, 1999 and entitled “DEVICE AND METHOD FOR DETERMINING ANALYTELEVELS”; U.S. Pat. No. 6,741,877 issued Feb. May 25, 2004 and entitled“DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS”; U.S. Pat. No.6,702,857 issued Feb. Mar. 9, 2004 and entitled “MEMBRANE FOR USE WITHIMPLANTABLE DEVICES”; and U.S. Pat. No. 6,558,321 issued Feb. May 6,2003 and entitled “SYSTEMS AND METHODS FOR REMOTE MONITORING ANDMODULATION OF MEDICAL DEVICES.” Methods and devices that are suitablefor use in conjunction with aspects of the preferred embodiments aredisclosed in U.S. application Ser. No. 10/991,353 filed Nov. 16, 2004and entitled “AFFINITY DOMAIN FOR ANALYTE SENSOR”; U.S. application Ser.No. 11/055,779 filed Feb. 9, 2005 and entitled “BIOINTERFACE WITHMACRO-AND-MICRO-ARCHITECTURE”; U.S. application Ser. No. 11/004,561filed Dec. 3, 2004 and entitled “CALIBRATION TECHNIQUES FOR A CONTINUOUSANALYTE SENSOR”; U.S. application Ser. No. 11/034,343 filed Jan. 11,2005 and entitled “COMPOSITE MATERIAL FOR IMPLANTABLE DEVICE”; U.S.application Ser. No. 09/447,227 filed Nov. 22, 1999 and entitled “DEVICEAND METHOD FOR DETERMINING ANALYTE LEVELS”; U.S. application Ser. No.11/021,046 filed Dec. 22, 2004 and entitled “DEVICE AND METHOD FORDETERMINING ANALYTE LEVELS”; U.S. application Ser. No. 09/916,858 filedJul. 27, 2001 and entitled “DEVICE AND METHOD FOR DETERMINING ANALYTELEVELS”; U.S. application Ser. No. 11/039,269 filed Jan. 19, 2005 andentitled “DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS”; U.S.application Ser. No. 10/897,377 filed Jul. 21, 2004 and entitled“ELECTROCHEMICAL SENSORS INCLUDING ELECTRODE SYSTEMS WITH INCREASEDOXYGEN GENERATION”; U.S. application Ser. No. 10/897,312 filed Jul. 21,2004 and entitled “ELECTRODE SYSTEMS FOR ELECTROCHEMICAL SENSORS”; U.S.application Ser. No. 10/838,912 filed May 3, 2004 and entitled“IMPLANTABLE ANALYTE SENSOR”; U.S. application Ser. No. 10/838,909 filedMay 3, 2004 and entitled “IMPLANTABLE ANALYTE SENSOR”; U.S. applicationSer. No. 10/838,658 filed May 3, 2004 and entitled “IMPLANTABLE ANALYTESENSOR”; U.S. application Ser. No. 11/034,344 filed Jan. 11, 2005 andentitled “IMPLANTABLE DEVICE WITH IMPROVED RADIO FREQUENCYCAPABILITIES”; U.S. application Ser. No. 10/896,772 filed Jul. 21, 2004and entitled “INCREASING BIAS FOR OXYGEN PRODUCTION IN AN ELECTRODESYSTEM”; U.S. application Ser. No. 10/789,359 filed Feb. 26, 2004 andentitled “INTEGRATED DELIVERY DEVICE FOR CONTINUOUS GLUCOSE SENSOR”;U.S. application Ser. No. 10/991,966 filed Nov. 17, 2004 and entitled“INTEGRATED RECEIVER FOR CONTINUOUS ANALYTE SENSOR”; U.S. applicationSer. No. 10/646,333 filed Aug. 22, 2003 and entitled “OPTIMIZED SENSORGEOMETRY FOR AN IMPLANTABLE GLUCOSE SENSOR”; U.S. application Ser. No.10/896,639 filed Jul. 21, 2004 and entitled “OXYGEN ENHANCING MEMBRANESYSTEMS FOR IMPLANTABLE DEVICES”; U.S. application Ser. No. 10/647,065filed Aug. 22, 2003 and entitled “POROUS MEMBRANES FOR USE WITHIMPLANTABLE DEVICES”; U.S. application Ser. No. 10/896,637 filed Jul.21, 2004 and entitled “ROLLED ELECTRODE ARRAY AND ITS METHOD FORMANUFACTURE”; U.S. application Ser. No. 09/916,711 filed Jul. 27, 2001and entitled “SENSOR HEAD FOR USE WITH IMPLANTABLE DEVICE”; U.S.application Ser. No. 11/021,162 filed Dec. 22, 2004 and entitled “SENSORHEAD FOR USE WITH IMPLANTABLE DEVICES”; U.S. application Ser. No.11/007,920 filed Dec. 8, 2004 and entitled “SIGNAL PROCESSING FORCONTINUOUS ANALYTE SENSOR”; U.S. application Ser. No. 10/695,636 filedOct. 28, 2003 and entitled “SILICONE COMPOSITION FOR BIOCOMPATIBLEMEMBRANE”; U.S. application Ser. No. 11/038,340 filed Jan. 18, 2005 andentitled “SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA”; U.S.application Ser. No. 11/007,635 filed Dec. 7, 2004 and entitled “SYSTEMSAND METHODS FOR IMPROVING ELECTROCHEMICAL ANALYTE SENSORS”; U.S.application Ser. No. 10/885,476 filed Jul. 6, 2004 and entitled “SYSTEMSAND METHODS FOR MANUFACTURE OF AN ANALYTE-MEASURING DEVICE INCLUDING AMEMBRANE SYSTEM”; U.S. application Ser. No. 10/648,849 filed Aug. 22,2003 and entitled “SYSTEMS AND METHODS FOR REPLACING SIGNAL ARTIFACTS INA GLUCOSE SENSOR DATA STREAM”; U.S. application Ser. No. 10/153,356filed May 22, 2002 and entitled “TECHNIQUES TO IMPROVE POLYURETHANEMEMBRANES FOR IMPLANTABLE GLUCOSE SENSORS”; U.S. application Ser. No.10/846,150 filed May 14, 2004 and entitled “ANALYTE MEASURING DEVICE”;U.S. application Ser. No. 10/842,716 filed May 10, 2004 and entitled“BIOINTERFACE MEMBRANES INCORPORATING BIOACTIVE AGENTS”; U.S.application Ser. No. 10/657,843 filed Sep. 9, 2003 and entitled “DEVICEAND METHOD FOR DETERMINING ANALYTE LEVELS”; U.S. application Ser. No.10/768,889 filed Jan. 29, 2004 and entitled “MEMBRANE FOR USE WITHIMPLANTABLE DEVICES”; U.S. application Ser. No. 10/633,367 filed Aug. 1,2003 and entitled “SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSORDATA”; U.S. application Ser. No. 10/632,537 filed Aug. 1, 2003 andentitled “SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA”; U.S.application Ser. No. 10/633,404 filed Aug. 1, 2003 and entitled “SYSTEMAND METHODS FOR PROCESSING ANALYTE SENSOR DATA”; U.S. application Ser.No. 10/633,329 filed Aug. 1, 2003 and entitled “SYSTEM AND METHODS FORPROCESSING ANALYTE SENSOR DATA”; and U.S. application Ser. No.60/660,743, filed on Mar. 10, 2005 and entitled “SYSTEMS AND METHODS FORPROCESSING ANALYTE SENSOR DATA FOR SENSOR CALIBRATION.”

All references cited herein, including but not limited to published andunpublished applications, patents, and literature references, and alsoincluding but not limited to the references listed in the Appendix, areincorporated herein by reference in their entirety and are hereby made apart of this specification. To the extent publications and patents orpatent applications incorporated by reference contradict the disclosurecontained in the specification, the specification is intended tosupersede and/or take precedence over any such contradictory material.

The term “comprising” as used herein is synonymous with “including,”“containing,” or “characterized by,” and is inclusive or open-ended anddoes not exclude additional, unrecited elements or method steps.

All numbers expressing quantities of ingredients, reaction conditions,and so forth used in the specification are to be understood as beingmodified in all instances by the term “about.” Accordingly, unlessindicated to the contrary, the numerical parameters set forth herein areapproximations that may vary depending upon the desired propertiessought to be obtained. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of anyclaims in any application claiming priority to the present application,each numerical parameter should be construed in light of the number ofsignificant digits and ordinary rounding approaches.

The above description discloses several methods and materials of thepresent invention. This invention is susceptible to modifications in themethods and materials, as well as alterations in the fabrication methodsand equipment. Such modifications will become apparent to those skilledin the art from a consideration of this disclosure or practice of theinvention disclosed herein. Consequently, it is not intended that thisinvention be limited to the specific embodiments disclosed herein, butthat it cover all modifications and alternatives coming within the truescope and spirit of the invention.

What is claimed is:
 1. A transcutaneous analyte sensor, the sensorcomprising: a non-planar wire comprising an insulator coating, whereinthe insulator coated wire comprises: a distal portion comprising adistal tip and an electrochemically reactive surface of the wire,wherein the distal portion is configured for insertion into a host; aproximal portion comprising a proximal tip and at least one portion ofthe wire exposed for electronic connection to an electronic device thatremains external to the host; and an intermediate portion locatedbetween the distal portion and the proximal portion, wherein theintermediate portion is configured for absorbing mechanical stressescaused by motion of the host, wherein a hardness and/or a modulus ofelasticity of each of the distal, intermediate and proximal portions aredifferent, whereby a stiffness of each of the distal, intermediate andproximal portions are different from physical or chemical processing ofthe insulator coated wire; and a multi-domain membrane covering theelectrochemically reactive surface of the wire.
 2. The sensor of claim1, wherein analyte is glucose.
 3. The sensor of claim 1, wherein each ofthe distal portion, the intermediate portion, and the proximal portionare configured to bend after sensor insertion.
 4. The sensor of claim 1,wherein the intermediate portion is configured to absorb a relativemovement between the distal portion and the proximal portion.
 5. Thesensor of claim 1, wherein the electronic device comprises a housingadapted for mounting on a skin of a host, wherein the housing compriseselectrical contacts configured for electrical connection to theelectronic connection of the proximal portion of the sensor, where theproximal portion has a preselected stiffness to maintain a stableconnection between the sensor and the electrical contacts.
 6. The sensorof claim 1, wherein the distal portion of the sensor has a preselectedflexibility to absorb mechanical stresses caused by motion of the host.7. The sensor of claim 1, wherein a stiffness of the proximal portion ofthe sensor is greater than a stiffness of distal portion of the sensor.